title: Immunovirological studies of fatal infectious mononucleosis in a patient with X-linked lymphoproliferative syndrome treated with intravenous immunoglobulin and interferon-alpha.
abstract: We have studied a 19-year-old male with X-linked lymphoproliferative syndrome (XLP) and infectious mononucleosis (IM) who was treated with high-dose immunoglobulin (500 mg/kg/day) and recombinant interferon (IFN)-alpha (2 x 10(6) IU/m2/day). Fulminant hepatitis was delayed; however, virus-associated hemophagocytic syndrome, cholestatic jaundice, and renal failure occurred terminally. Initially, nonspecific natural killer (NK) cell activity against K562 cells was normal but it gradually decreased. Although reactive T cells were markedly increased in his blood during the acute phase, spontaneous EBV-positive cell lines were easily established. Additionally, his mononuclear cells produced IFN-gamma but not IFN-alpha prior to treatment. Based on results of in vitro studies, we conclude that both IFN-alpha and IFN-gamma production are likely necessary for inhibiting EBV immortalization in vitro. Both IFN-alpha and -gamma were produced in cultures of B95-8 EBV-infected mononuclear cells from EBV-seropositive healthy individuals. These results suggest that defective EBV-specific cytotoxic T cell activity accompanied with defective or discordant IFN-alpha and -gamma production permitted the development of fatal IM in this patient. Combined treatment with immunoglobulin and IFN-alpha appeared to be partially effective during the early stage of this disease.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68105-1065.
authors.forename: M
authors.initials: M
authors.lastname: Okano
authors.forename: S J
authors.initials: SJ
authors.lastname: Pirruccello
authors.forename: H L
authors.initials: HL
authors.lastname: Grierson
authors.forename: D R
authors.initials: DR
authors.lastname: Johnson
authors.forename: G M
authors.initials: GM
authors.lastname: Thiele
authors.forename: D T
authors.initials: DT
authors.lastname: Purtilo
mesh_terms: D000328:Adult; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007136:Immunoglobulins / Q000008:administration & dosage*; D007244:Infectious Mononucleosis / Q000382:microbiology* / Q000628:therapy; D007275:Injections, Intravenous; D007370:Interferon Type I / Q000627:therapeutic use*; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000628:therapy; D008297:Male; D011994:Recombinant Proteins; D014960:X Chromosome
chemical_list: D007136:Immunoglobulins; D007370:Interferon Type I; D011994:Recombinant Proteins